Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.
For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.
3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.
3 to 4 grams L-phenylalanine or 150 to 200 mg of DL-phenylalanine daily
In one study, depressed people given L-phenylalanine experienced results comparable to those produced by an antidepressant.
L-phenylalanine is another amino acid that converts to mood-affecting substances (including phenylethylamine and norepinephrine). Preliminary research reported that L-phenylalanine improved mood in most of the depressed people studied.1 DLPA is a mixture of the essential amino acid L-phenylalanine and its synthetic mirror image, D-phenylalanine. DLPA (or the D- or L- form alone) reduced depression in 31 of 40 people in a preliminary trial.2 Some doctors suggest a one-month trial with 3–4 grams per day of phenylalanine for people with depression, although some researchers have found that even very low amounts—75–200 mg per day—were helpful in preliminary trials.3 In one double-blind trial, depressed people given 150–200 mg of DLPA per day experienced results comparable to that produced by an antidepressant drug.4
Low Back Pain
1,500 to 2,500 mg per day of DL-Phenylalanine
Several studies suggest that a synthetic version of phenylalanine called D-phenylalaline, may reduce pain by decreasing the enzyme that breaks down endorphins.
Several animal studies and some research involving humans suggest that a synthetic version of the natural amino acid phenylalanine called D-phenylalaline (DPA), reduces pain by decreasing the enzyme that breaks down endorphins.5 It is less clear whether DPA may help people with LBP, though there are a small number of reports to that effect,6 including one uncontrolled report of 27 of 37 people with LBP experiencing “good to excellent relief.”7 In a double-blind trial, University of Texas researchers found that 250 mg of DPA four times per day for four weeks was no more effective than placebo for 30 people with various types of chronic pain; 13 of these people had low back pain.8 In a Japanese clinical trial, 4 grams of DPA per day was given to people with chronic low back pain half an hour before they received acupuncture.9 Although not statistically significant, the results were good or excellent for 18 of the 30. The most common supplemental form of phenylalanine is D,L-phenylalanine (DLPA). Doctors typically recommend 1,500–2,500 mg per day of DLPA.
1,500 mg daily
D-phenylalanine (DPA) decreases pain by blocking the enzymes that break down the body’s natural painkillers. Clinical studies suggest DPA may inhibit some types of chronic pain.
Certain amino acids have been found to raise pain thresholds and increase tolerance to pain. One of these, a synthetic amino acid called D-phenylalanine (DPA), decreases pain by blocking the enzymes that break down endorphins and enkephalins, the body’s natural pain-killing chemicals.10 , 11 DPA may also produce pain relief by other mechanisms, which are not well understood.12
In animal studies, DPA decreased chronic pain within 15 minutes of administration and the effects lasted up to six days.13 It also decreased responses to acute pain. These findings have been independently verified in at least five other studies.14 , 15 Clinical studies on humans suggest DPA may inhibit some types of chronic pain, but it has little effect on most types of acute pain.16 , 17
Most human research has tested the pain-relieving effects of 750 to 1,000 mg per day of DPA taken for several weeks of continuous or intermittent use. The results of this research have been mixed, with some trials reporting efficacy,18 , 19 , 20 others reporting no difference from placebo,21 and some reporting equivocal results.22 It appears that DPA may only work for some people, but a trial period of supplementation seems worthwhile for many types of chronic pain until more is known. If DPA is not available, a related product, D,L-phenylalanine (DLPA), may be substituted at amounts of 1,500 to 2,000 mg per day.
As early as 1981, preliminary human research showed that DPA made the pain-inhibiting effects of acupuncture stronger.23 One controlled animal study24 and two controlled trials in humans25 , 26 showed that DPA taken the day before acupuncture increased the effectiveness of acupuncture in reducing both acute dental and chronic low back pain.
Consult a qualified healthcare practitioner
In one trial, D-phenylalanine (DPA) supplementation improved motor control and tremors in people with Parkinson’s disease. DPA should not be taken with L-dopa as it may interfere with the transport of L-dopa to the brain.
In a small, four-week trial, D-phenylalanine (DPA) supplementation improved motor control and tremors in people with Parkinson’s disease.27 Additional research is needed before the benefits of this treatment can be considered proven. DPA should not be taken with L-dopa as it may interfere with the transport of L-dopa to the brain.28 People with Parkinson’s disease should consult with a physician before using DPA. Some commercially available phenylalanine products contain a 50:50 mixture of DPA and LPA, the form of phenylalanine that occurs naturally in food (these products are known as DLPA). People with Parkinson’s disease should consult a physician before using DPA or DLPA.
50 mg daily per 2.2 lbs (1 kg) of body weight, with ultraviolet light exposure
L-phenylalanine, in conjunction with ultraviolet light exposure, may improve repigmentation of skin.
Supplementation with the amino acid L-phenylalanine (LPA) may have value when combined with ultraviolet (UVA) light therapy. Several clinical trials, including one double-blind trial, indicated that LPA (50 mg per 2.2 pounds of body weight per day—3,500 mg per day for a 154-pound person—or less) increased the extent of repigmentation induced by UVA therapy. LPA alone also produced a more modest repigmentation in some people.29 A study of vitiligo in children reported that LPA plus UVA was an effective treatment in a majority of the children.30
A group of Spanish doctors reported on their experience using LPA over a six-year period. Some of the 171 people with vitiligo received LPA (50 or 100 mg per 2.2 pounds body weight per day) for up to three years. Between April and October of each year, participants also applied a 10% LPA gel, prior to exposing their skin to the sun for 30 minutes. Some improvement was seen in 83% of participants, and the results were rated as good in 57% (75% improvement or better).31
Alcohol Withdrawal (Glutamine, L-Tyrosine, Multivitamin, Tryptophan)
Refer to label instructions
In double-blind research, alcoholics treated with L-tyrosine combined with DLPA (D,L-phenylalanine), L-glutamine, prescription L-tryptophan, plus a multivitamin had reduced withdrawal symptoms and decreased stress.
Kenneth Blum and researchers at the University of Texas have examined neurotransmitter deficiencies in alcoholics. Neurotransmitters are the chemicals the body makes to allow nerve cells to pass messages (of pain, touch, thought, etc.) from cell to cell. Amino acids are the precursors of these neurotransmitters. In double-blind research, a group of alcoholics were treated with 1.5 grams of D,L-phenylalanine (DLPA), 900 mg of L-tyrosine, 300 mg of L-glutamine, and 400 mg of L-tryptophan (now available only by prescription) per day, plus a multivitamin-mineral supplement.32 This nutritional supplement regimen led to a significant reduction in withdrawal symptoms and decreased stress in alcoholics compared to the effects of placebo.
Refer to label instructions
Supplementing with D-phenylalanine (DPA) has been shown to reduce chronic pain due to OA. DPA inhibits the enzyme that breaks down some of the body’s natural painkillers.
Supplementation with D-phenylalanine (DPA), a synthetic variation of the amino acid, L-phenylalanine (LPA), has reduced chronic pain due to OA in a preliminary trial.33 In that study, participants took 250 mg three to four times per day, with pain relief beginning in four to five weeks. Other preliminary trials have confirmed the effect of DPA in chronic pain control,34 but a double-blind trial found no benefit.35 DPA inhibits the enzyme that breaks down some of the body’s natural painkillers, substances called enkephalins, which are similar to endorphins. An increase in the amount of enkephalins may explain the reported pain-relieving effect of DPA. If DPA is not available, a related product, D,L-phenylalanine (DLPA), may be substituted (1,500 to 2,000 mg per day). Phenylalanine should be taken between meals, because protein found in food may compete for uptake of phenylalanine into the brain, potentially reducing its effect.36
Refer to label instructions
D-phenylalanine has been used with mixed results to treat chronic pain, including pain caused by rheumatoid arthritis.
D-phenylalanine has been used with mixed results to treat chronic pain, including pain caused by RA.37 No research has evaluated the effectiveness of DL-phenylalanine, a related supplement, in treating people with RA. The effect of either form of phenylalanine in the treatment of people with RA remains unproven.
DLPA has been used in amounts ranging from 75–1,500 mg per day. This compound can have powerful effects on mood and on the nervous system, and therefore DLPA should be taken only under medical supervision. LPA has been used in amounts up to 3.5 grams per day. For best results, phenylalanine should be taken between meals, because the protein present in food can interfere with the uptake of phenylalanine into the brain, potentially reducing its effect.
LPA is found in most foods that contain protein. DPA does not normally occur in food. However, when phenylalanine is synthesized in the laboratory, half appears in the L-form and the other half in the D-form. These two compounds can also be synthesized individually, but it is more expensive to do so. The combination supplement (DLPA) is often used because of the lower cost and because both components exert different health-enhancing effects.
People whose diets are very low in protein may develop a deficiency of LPA, although this is believed to be very uncommon. However, one does not necessarily have to be deficient in LPA in order to benefit from a DLPA supplement.
People with phenylketonuria must not supplement with phenylalanine.
Some research suggests that people with tardive dyskinesia may process phenylalanine abnormally. Until more is known, it makes sense for people with this condition to avoid phenylalanine supplementation.
LPA competes with several other amino acids for uptake into the body and the brain. Therefore, for best results, phenylalanine should be taken between meals, or away from protein-containing foods. People taking prescription or over-the-counter medications should consult a physician before taking DLPA.
The maximum amount of DLPA that is safe is unknown. However, consistent toxicity in healthy people has not been reported with 1,500 mg per day or less of DLPA, except for occasional nausea, heartburn, or transient headaches.
When 100 mg of LPA per 2.2 pounds body weight or more was given to animals, a variety of complex problems occurred, leading two researchers to have concerns about potential toxicity of high amounts in humans.38 While these concerns were directed at LPA specifically, they are likely to be equally applicable to DLPA. Although no serious adverse effects have been reported in humans taking phenylalanine, amounts greater than 1,500 mg per day should be supervised by a doctor.
1. Sabelli HC, Fawcett J, Gustovsky F, et al. Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiatry 1986;47:66–70.
2. Sabelli HC, Fawcett J, Gustovsky F, et al. Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiatry 1986;47:66–70.
3. Beckmann H, Strauss MA, Ludolph E. DL-Phenylalanine in depressed patients: an open study. J Neural Transm 1977;41:123–34.
4. Beckmann H, Athen D, Olteanu M, Zimmer R. DL-phenylalanine versus imipramine: a double-blind controlled study. Arch Psychiatr Nervenkr 1979;227:49–58.
5. Ehrenpreis S. Analgesic properties of enkephalinase inhibitors: animal and human studies. Prog Clin Biol Res 1985;192:363–70 [review].
6. Balagot RC, Ehrenpreis S, Kubota K, Greenberg J. Advances in Pain Research and Therapy, Vol 5, Bonica JJ, Liebsekind JC, Albe-Fessard DG (eds), Raven Press, New York, 1983, 289–93.
7. Gaby AR. Editor’s Corner. Northwest Acad Prev Med 1983;July:3, 5, 8.
8. Walsh NE, Ramamurthy S, Schoenfeld L, Hoffman J. Analgesic effectiveness of d-phenylalanine in chronic pain patients. Arch Phys Med Rehabil 1986;67:436–9.
9. Kitade T, Odahara Y, Shinohara S, et al. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (2nd report)—schedule of administration and clinical effects in low back pain and tooth extraction. Acupunct Electrother Res 1990;15:121–35.
10. Ehrenpreis S. Analgesic properties of enkephalinase inhibitors: animal and human studies. Prog Clin Biol Res 1985;192:363–70.
11. Guisti P, Carrara M, Cima L, Borin G. Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine. Eur J Pharmacol 1985;116:287–92.
12. Walsh NE, Ramamurthy S, Schoenfeld LS, Hoffman J. D-phenylalanine was not found to exhibit opiod receptor mediated analgesia in monkeys. Pain 1986;26:409–10.
13. Ehrenpreis S, Balagot R, Comaty JE, Myles SB. Naloxonr reversible analgesia in mice produced by D-phenylalanine and hydrocinnamic acid, inhibitors of carboxypeptidase A. In Bonica JJ, et al., eds. Advances in Pain Research and Therapy, Vol. 3. New York: Raven Press, 1979.
14. Ehrenpreis S. Pharmacology of enkephalinase inhibitors: animal and human studies. Acupunct Electrother Res. 1985;10:203–8.
15. Balagot RC, Ehrenpreis S, Kubota K, Greenberg J. Analgesia in mice and humans by D-phenylalanine: relation to inhibition of enkephalin degradation amd enkephalin levels. In Bonica JJ, et al., eds. Advances in Pain Research and Therapy, Vol. 5. New York: Raven Press, 1983
16. Mitchell MJ, Daines GE, Thomas BL. Effect of L-tryptophan and phenylalanine on burning pain threshold. Phys Ther 1987;67:203–5.
17. D’Alessandro R. D-Phenylalanine does not affect nociceptive, flexion reflex thresholds in normal humans. Anesth Analg 1983;62:857–8.
18. Budd K. Use of D-phenylalanine, an enkephalinase inhibitor, in the treatment of intractable pain. In Bonica JJ, et al., eds. Advances in Pain Research and Therapy, Vol. 5. New York: Raven Press, 1983.
19. Donzelle G, Bernard L, Deumier R, et al. Curing trial of complicated oncologic pain by D-phenylalanine. Anesthesie, Analgesie, Reanimation 1981;38:655–8 [in French].
20. Balagot RC, Ehrenpreis S, Kubota K, Greenberg J. Analgesia in mice and humans by D-phenylalanine: relation to inhibition of enkephalin degradation and enkephalin levels. In Bonica JJ, et al., eds. Advances in Pain Research and Therapy, Vol. 5. New York: Raven Press, 1983.
21. Walsh NE, Ramamurthy S, Schoenfeld LS, Hoffman J. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil 1986;67:436–9.
22. Sicuteri F. Enkephalinase inhibition relieves pain syndromes of central dysnociception (migraine and related headache). Cephalalgia 1981;1:229–32.
23. Kitade T, Minamikawa M, Nawata T, et al. An experimantal study on the enhancing effects of phenylalanine on acupuncture analgesia. Am J Chin Med 1981;9:243–8.
24. Takeshige C, Mera H, Hisamitsu T, et al. Inhibition of the analgesia inhibitory system by D-phenylalanine and proglumide. Brain Res Bull 1991;26:385–91.
25. Kitade T, Odahara Y, Shinohara S, et al. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (first report)—effect on pain threshold and inhibition by naloxone. Acupunct Electrother Res 1988;13:87–97.
26. Kitade T, Odahara Y, Shinohara S, et al. Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia bu D-phenylalanine (2nd report)—schedule of administration and clinical effects in low back pain and tooth extraction. Acupunct Electrother Res 1990;15:121–35.
27. Heller B, Fischer E, Martin R. Therapeutic action of D-phenylalanine in Parkinson’s disease. Arzneimittelforschung 1976;26:577–9.
28. Wurtman RJ, Wurtman JJ, eds. Nutrition and the Brain, vol 7. New York: Raven Press, 1986.
29. Siddiqui AH, Stolk LM, Bhaggoe R, et al. L-phenylalanine and UVA irradiation in the treatment of vitiligo. Dermatology 1994;188:215–8.
30. Schulpis CH, Antoniou C, Michas T, Strarigos J. Phenylalanine plus ultraviolet light: preliminary report of a promising treatment for childhood vitiligo. Pediatr Dermatol 1989;6:332–5.
31. Camacho F, Mazuecos J. Treatment of vitiligo with oral and topical phenylalanine: 6 years of experience. Arch Dermatol 1999;135:216–7.
32. Blum K. A commentary on neurotransmitter restoration as a common mode of treatment for alcohol, cocaine and opiate abuse. Integr Psychiatr 1986;6:199–204.
33. Balagot RC, Ehrenpreis S, Kubota K, Greenberg J. Analgesia in mice and humans by D-phenylalanine: Relation to inhibition of enkephalin degradation and enkephalin levels. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG, eds., Advances in Pain Research and Therapy, Vol 5. New York: Raven Press, 1983, 289–93.
34. Budd K. Use of D-phenylalanine, an enkephalinase inhibitor, in the treatment of intractable pain. In: Bonica JJ, Liebeskind JC, Albe-Fessard DG, eds., Advances in Pain Research and Therapy, Vol 5. New York: Raven Press, 1983, 305–8.
35. Walsh NE, Ramamurthy S, Schoenfeld LS, Hoffman J. Analgesic effectiveness of D-phenylalanine in chronic pain patients. Arch Phys Med Rehabil 1986;67:436–9.
36. Seltzer S, Marcus R, Stoch R. Perspectives in the control of chronic pain by nutritional manipulation. Pain 1981;11:141–8 [review].
37. Balagot RC, Ehrenpreis S, Kubota K, et al. Analgesia in mice and humans by D-phenylalanine: Relation to inhibition of enkephalin degradation and enkephalin levels. Adv Pain Res Ther 1983;5:289–93.
38. Burkhart CG, Burkhart CN. Phenylalanine with UVA for the treatment of vitiligo needs more testing for possible side effects. J Am Acad Dermatol 1999;40:1015 [letter].
Last Review: 11-07-2012
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The information presented in Aisle7 is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2013.
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